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Proline-Directed Androgen Receptor Phosphorylation.

Gao Y, Chen S - J Mol Genet Med (2013)

Bottom Line: The androgen receptor (AR) has been identified for decades and mediates essential steroid functions.This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on proline-directed serine/threonine phosphorylation that occurs predominantly on the receptor.The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School 330 Brookline, MA 02115, USA.

ABSTRACT

The androgen receptor (AR) has been identified for decades and mediates essential steroid functions. Like most of biological molecules, AR functional activities are modulated by post-translational modifications. This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on proline-directed serine/threonine phosphorylation that occurs predominantly on the receptor. The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens.

No MeSH data available.


Related in: MedlinePlus

A typical mass-spec analysis in AR study. LNCaP cells in androgen-deprived medium were treated with DHT (dihydrotestosterone) and AR was harvested by Co-IP (Co-immunoprecipitation) for mass-spec analysis that was aligned to human AR (GenBank: M23263.1). Highlighted are identified phosphorylation corresponding to Ser94 and Ser650(GenBank: M20132.1), with Ser424 at lower frequency. Phosphorylation on Ser81 is not identified, likely due to its particular location that affects fragmentation during processing.
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Figure 2: A typical mass-spec analysis in AR study. LNCaP cells in androgen-deprived medium were treated with DHT (dihydrotestosterone) and AR was harvested by Co-IP (Co-immunoprecipitation) for mass-spec analysis that was aligned to human AR (GenBank: M23263.1). Highlighted are identified phosphorylation corresponding to Ser94 and Ser650(GenBank: M20132.1), with Ser424 at lower frequency. Phosphorylation on Ser81 is not identified, likely due to its particular location that affects fragmentation during processing.

Mentions: Next, we will concentrate on three Pro-directed Ser residues (Ser81, Ser94, and Ser650) that are most robustly phosphorylated based on multiple phosphoamino acid and mass-specanalyses (Figure 2) [12,14]. Although Ser81 is apparently the highest androgen-stimulated AR phosphorylation residues, this event cannot be readily captured by mass-spec due to its particular embedment in the Poly-Q stretch that would compromise the fragmentation efficiency during digestion and processing (Figure 2 and 3) [17].


Proline-Directed Androgen Receptor Phosphorylation.

Gao Y, Chen S - J Mol Genet Med (2013)

A typical mass-spec analysis in AR study. LNCaP cells in androgen-deprived medium were treated with DHT (dihydrotestosterone) and AR was harvested by Co-IP (Co-immunoprecipitation) for mass-spec analysis that was aligned to human AR (GenBank: M23263.1). Highlighted are identified phosphorylation corresponding to Ser94 and Ser650(GenBank: M20132.1), with Ser424 at lower frequency. Phosphorylation on Ser81 is not identified, likely due to its particular location that affects fragmentation during processing.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389684&req=5

Figure 2: A typical mass-spec analysis in AR study. LNCaP cells in androgen-deprived medium were treated with DHT (dihydrotestosterone) and AR was harvested by Co-IP (Co-immunoprecipitation) for mass-spec analysis that was aligned to human AR (GenBank: M23263.1). Highlighted are identified phosphorylation corresponding to Ser94 and Ser650(GenBank: M20132.1), with Ser424 at lower frequency. Phosphorylation on Ser81 is not identified, likely due to its particular location that affects fragmentation during processing.
Mentions: Next, we will concentrate on three Pro-directed Ser residues (Ser81, Ser94, and Ser650) that are most robustly phosphorylated based on multiple phosphoamino acid and mass-specanalyses (Figure 2) [12,14]. Although Ser81 is apparently the highest androgen-stimulated AR phosphorylation residues, this event cannot be readily captured by mass-spec due to its particular embedment in the Poly-Q stretch that would compromise the fragmentation efficiency during digestion and processing (Figure 2 and 3) [17].

Bottom Line: The androgen receptor (AR) has been identified for decades and mediates essential steroid functions.This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on proline-directed serine/threonine phosphorylation that occurs predominantly on the receptor.The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School 330 Brookline, MA 02115, USA.

ABSTRACT

The androgen receptor (AR) has been identified for decades and mediates essential steroid functions. Like most of biological molecules, AR functional activities are modulated by post-translational modifications. This review is focused on the reported activities and significance of AR phosphorylation, with particular emphasis on proline-directed serine/threonine phosphorylation that occurs predominantly on the receptor. The marked enrichment of AR phosphorylation in the most diverse N-terminal domain suggests that targeting AR phosphorylation can be synergistic to antagonizing the C-terminal domain by clinical antiandrogens.

No MeSH data available.


Related in: MedlinePlus